1. Field of the Invention
The present invention relates generally to feline healthcare and particularly to prevention, treatment and management of stomatitis, most particularly feline chronic gingivo-stomatitis (FCGS). More particularly, aspects of the invention relate to manufacture and use of orally administered pharmaceutical preparations for prevention, treatment and management of feline chronic gingivo-stomatitis (FCGS).
2. Description of Related Art
For these purposes, “stomatitis” refers generically to any oropharyngeal inflammation and related processes of the mucous membranes in or around the mouth and oropharyngeal tissues of a subject. When stomatitis involves inflammation of the gums (i.e., gingiva), it can be generally referred to as gingivo-stomatitis, irrespective of whether mucous membranes other than the gums are also inflamed. To make more specific reference to inflammation of the gums, however, it is sometimes referred to as just “gingivitis.” Because of the critical association between the gums and dental hygiene, for which numerous consumer products are targeted, at least for human healthcare markets, most consumers are somewhat familiar with the “gingivitis” term, although any form of gingivo-stomatitis can lead to serious complications.
Although the risks and challenges of gingivo-stomatitis can be serious for any species, gingivo-stomatitis can be especially devastating in feline populations. The “chronic” aspect of FCGS applies if a cat's natural healing mechanisms are unable to reverse the condition, which is often presumed if a cat's gingivo-stomatitis does not resolve within thirty days of onset or initial diagnosis. Once the condition progresses to a chronic condition, then, unfortunately, the prognosis for cats with FCGS tends to be life changing. Many veterinarians routinely consider full mouth dental extraction and root removal as the most practical treatment for, possibly even an essential part of, managing FCGS.
Though domestic cats can often live long lives despite dental extraction, the resulting lifestyle limitations can be life altering. A cat's teeth are not only important for eating, but also for self-defense. Moreover, their teeth often play an important role in their social relationships, especially with male cats, as a male cat will typically use its teeth to hold onto the neck of a female cat during copulation. Other challenges can be understood from published scientific literature on the subject, such as the December 2010 article entitled “The Disease Formerly Known as Lymphocytic/Plasmacytic Gingivo-Stomatitis,” which can be accessed on the Internet through the website located at URL www.toothvet.ca, which is incorporated herein in its entirety by this reference.
Despite the well-known and long-felt needs for developing a pharmaceutical intervention for FCGS, no pharmaceutical interventions have demonstrated sufficient efficacy to be recognized as a routine intervention option for veterinarians. Moreover, even if one were contemplating active ingredients for preventing, treating or managing FCGS without the benefit of the present invention and impermissible hindsight, the teachings of the present invention would not be realistic candidates. Not only are Applicant's present teachings not known to be efficacious in the art of treating FCGS, but such teachings would likely be summarily dismissed from consideration even if a related thought ever arose. Such summarial dismissal would seem inevitable, largely because, if for no other reason, many have assumed that some aspects of the present invention present a material risk of ulcerating oropharyngeal tissues.
Irrespective of the state of art in the present field, for some applications far outside the scope and field of the present invention, rapamycin (also known as sirolimus) is a well-known pharmaceutical agent. Most notably, rapamycin has long been successfully used to minimize organ transplant rejection in humans, while seemingly countless other potential applications have also been postulated from time to time.
Rapamycin and its numerous analogs and derivatives (collectively known as “rapalogs”) famously act to inhibit its namesake metabolic pathway in mammals—the mammalian target of rapamycin (“mTOR”). The critical metabolic roles of the mTOR pathway have long led to broad speculation about possible medical uses for rapamycin and rapalogs, in addition to rapamycin's well-known efficacy in reducing human organ transplant rejection. However, despite the success with prevention of transplant rejection, and despite the many long-felt needs and corresponding tremendous efforts in developing rapamycins for other indications, effective use of rapamycin or other rapalogs for treating or preventing other disorders has not been widely successful and has been very limited at best. The reader should refer to the Related UT Application, which has been incorporated by reference, for additional technical descriptions and a detailed description that relates to fields other than organ transplant.
Particular formulations taught in the Related UT Application (the “2008 Discoveries”) provided particles or “cores” containing the active rapamycin ingredient, and those cores were microencapsulated within a protective polymer matrix, for oral administration of the rapamycin. The rapamycin cores were preferably microencapsulated using a spinning disk atomization coating process with a protective polymer matrix known under the “EUDRAGIT® S 100” name. The EUDRAGIT® S 100 polymer matrix principally consists of a particular methacrylate polymer that is generally stable at pH levels below 7 and was thought to protect rapamycin from degrading in acidic conditions of the stomach. Then, once the microencapsulated rapamycin entered neutral or basic conditions (i.e., pH greater than or equal to 7) within the intestines, the protective matrix would be able to dissolve and, theoretically, un-degraded rapamycin would then be bioavailable for absorption through the intestinal walls of the subject. However, despite tremendous hope for broad efficacy of orally administered use of such microencapsulated rapamycin preparations, and despite widespread national and international attention to the 2008 Discoveries, commercial acceptance of the 2008 Discoveries has been minimal if not non-existent, as formidable challenges have remained.
Still, though, referring again to the field of the present invention, there remain long-felt unresolved needs in improving feline healthcare by providing an efficacious pharmaceutical preparation for treating and otherwise managing FCGS. Many other secondary needs and objectives will be understood by those of skill in the art.